The objective of this proposal is to describe and characterize at the molecular level the effects of aging on the substrate hydroxylation activities, composition, catalytic efficiency and regulation of drug metabolism systems. We will focus initially on the liver and colon drug metabolism systems which have been shown to decrease and increase, respectively, in activity with age. We will approach these goals by examining the effects of age on the rate of hydroxylation of N- and O-methyl drugs, polycyclic hydrocarbons, alkanes and fatty acids by liver and colon microsomes. We will examine the response of these activities to inducers and inhibitors as a function of age and correlate the effects of these perturbations on cytochrome P-450 specific content and cytochrome P-450 reductase specific activity. We will solubilize, resolve and characterize cytochrome P-450 and reductase from rat and colon microsomes as a function of age. We feel these age-dependent changes in drug metabolism will give insight into the development of a more appropriate drug therapy for older individuals and will aid in our understanding of age-related shifts in how various organs metabolize drugs.